Clinical Description
Multiple myeloma is a cancer of the plasma cell, a type of lymphocyte that produces antibodies, proteins that normally fight infections. These abnormal plasma cells proliferate and accumulate in the bone marrow, thereby interfering with normal bone marrow function. Furthermore, instead of producing normal, fully formed antibodies to fight infections like normal plasma cells do, these abnormal plasma cells secrete abnormally large amounts of a single type of protein (“monoclonal immunoglobulin”) derived from one cell population (“monoclonal”). The plasma cells continuously make these proteins. These proteins may directly harm the kidney, or deposit in the kidneys and cause kidney disease. The abnormal myeloma cells also produce chemicals that stimulate other cells to dissolve bone. This causes bones to develop “holes”, or lytic lesions.
There are several types of myeloma. Most cases have multiple marrow sites and the term “multiple myeloma” is used. Solitary plasmacytoma is when only one site is evident, and extramedulluary myeloma is when tissues other than marrow are involved. Tumors of plasma cells are known as plasmacytomas.
Symptoms of Multiple Myeloma
Since multiple myeloma often involves bone lesions, the most common early symptom of multiple myeloma is bone pain, which usually occurs in the lower back or ribs but may involve any bone. The bone lesions release calcium into the blood, and can cause high calcium levels. Since the abnormal plasma cells in multiple myeloma produce proteins in an uncontrolled manner which can cause kidney dysfunction, patients may experience symptoms of kidney failure, such as fatigue, decreased urination and swelling of the feet and legs.
Since multiple myeloma involves abnormal plasma cells that accumulate and crowd out the normal marrow, patients may have a marrow that does not function properly. This leads to patients having low red blood cell levels (anemia), and low levels of white blood cells and platelets. As a result, patients can experience fatigue, weakness and shortness of breath on exertion due to anemia, infections due to low white blood cell counts, and easy bruising, or nose or gum bleeding due to low platelets (small cells that help blood to clot).
Risk Factors of Multiple Myeloma
Myeloma rarely occurs in people younger than 40 yrs. Most cases occur after age 60. African-Americans have a higher rate of myeloma. Previous radiation and chemotherapy has not been shown to cause myeloma.
How Multiple Myeloma is Diagnosed.
Multiple myeloma can be diagnosed by examining the blood, urine and the bone marrow, and by X-rays of the skeleton. The diagnosis of multiple myeloma depends on finding increased bone marrow myeloma cells (malignant plasma cells) by bone marrow aspiration and biopsy, and either increased “monoclonal” proteins (“M” component) in the blood/urine, or bone lesions on X-ray.
Other tests may aid as well. Blood cell counts are measured and may show low red blood, white blood and platelet cell counts, showing the degree which to bone marrow is affected. Calcium due to bone destruction can be high, and the protein albumin may be low. Beta-2 microglobulin is a protein that is an indirect measure of the size and growth rate of myeloma. Lastly, kidney function is determined by blood tests.
Treatment Options for Multiple Myeloma at Tufts Medical Center
Patients should first be evaluated by a specialist to determine the stage of myeloma and the genes in the abnormal plasma cells. Some patients can have ‘smoldering’ myeloma – when the abnormal protein has been detected and there are more than 10% abnormal plasma cells in the bone marrow but there are no sympotms because there is no organ damage. Other patients can have “monoclonal gammopathy of undetermined significance” or MGUS when the abnormal protein is found but the percentage of abnormal plasma cell is less than 10%.
For the majority of patients, myeloma cannot be cured but it can become a chronic treatable disease. The goal of treatment is to prolong survival and prevent organ damage, thereby alleviating symptoms. Therapy with combinations of several drugs – including the new drugs bortezomib and lenalidomide -- is the mainstay. Most patients, even when they are older (up to 75 years old), should be considered for an autologous stem cell transplant when the myeloma is at a minimal stage following initial therapy. The stem cells are collected from the patient by a process called leukapheresis and returned after a round of high dose chemotherapy. This treatment is generally well-tolerated and can keep the myeloma in a remission for a number of years when followed by consolidation and maintenance therapy. In some patients this transplant can be repeated when the disease comes back.
When myeloma relapses, numerous standard and protocol based therapies are available at Tufts, including treatment with new monoclonal antibodies such as daratumumab and new agents such as selinexor. In addition, at Tufts an option for younger patients is to get a stem cell transplant from a sibling or unrelated donor.
Programs + Services
Tufts Medical Center's Hematologic Malignancies Program in Boston uses the latest techniques to pinpoint your cancer type and provide you with the most effective treatment.
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Research + Clinical Trials
The purpose of this study is to evaluate the safety of a step-up dosing approach (starting with low doses followed by higher doses) of the study medicine (elranatamab) in participants with multiple myeloma that has come back after responding to treatment or has not responded to treatment (relapsed/refractory multiple myeloma). This study will also look at the safety and efficacy of different doses of elranatamab, as well as different intervals between doses.
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The purpose of this study is to compare the efficacy of teclistamab-daratumumab (Tec-Dara) with daratumumab subcutaneously (SC) in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd). Teclistamab is an new drug that is being evaluated to treat participants with multiple myeloma, an incurable malignant plasma cell disorder. This is a multicenter, randomized, open-label, Phase 3 study in multiple myeloma patients who have previously received 1 to 3 prior line(s) of therapy including a PI and lenalidomide.
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In response to the significant need to intensify efforts at early diagnosis, this trial proposes further building on knowledge of the genetic basis of AL in clonal plasma cells. The main goal of this study is to screen for the diagnosis of light-chain amyloidosis (AL) before the onset of symptomatic disease.
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